Personalized Treatment of Recurrent, Metastatic Head and Neck Cancer Guided by Patient-Derived Xenograft Models.

Recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) is associated with a poor prognosis and short survival duration. There is an urgent need to identify personalized predictors of drug response to guide the selection of the most effective therapy for each individual recurrence. We tested the feasibility of patient-derived xenografts (PDX) for guiding their RMHNSCC salvage treatment. Fresh tumor samples from eligible, consented patients were implanted into mice. Established tumors were expanded in mouse PDX cohorts to identify responses to candidate salvage drug treatments in parallel testing. Patients alive and suitable for chemotherapy were treated based on responses determined by PDX testing. Nine patient tumors were successfully engrafted in mice with an average time of 89.2±41.7 days. Four patients' PDX models underwent parallel drug testing. Two patients received PDX-guided therapy. In one of these patients, single agents of cetuximab and paclitaxel demonstrated the best responses in the PDX model, and this patient exhibited sequential partial responses to each drug, including a 17-month clinical response to cetuximab. The main limitation of PDX testing for RMHNSCC was the time delay in obtaining testing results. Despite this, parallel PDX testing may be feasible for a subset of patients and appears to correlate with clinical benefit.

Assessment of urine colour using a wallet card: a randomised study of a novel patient self-care tool during chemoradiation for oesophageal cancer.

BACKGROUND: Patients undergoing neoadjuvant chemoradiation for oesophageal cancer often experience dehydration from decreased fluid intake and increased losses. Despite frequent clinical visits during treatment, patients can still present with dehydration, suggesting the need for increased patient awareness and engagement around adverse event management at home. Evidence for benefits of self-monitoring may help motivate patients to engage proactively in their own care to improve their treatment experience. METHODS: We performed a randomised single-centre study of a urine colour self-monitoring card (UCC) during chemoradiation therapy for oesophageal cancer, compared with standard dietitian counselling. Primary outcome was self-efficacy as determined by the Self-Management Resource Centre Self-Efficacy for Managing Chronic Disease Scale (SMCD). Secondary outcomes included Burge thirst scores, Edmonton Symptom Assessment System scores (ESAS), patient-initiated hydrations, creatinine rise and satisfaction with the UCC. RESULTS: Thirty-five patients were randomised. UCC use was not associated with improved SMCD or ESAS scores compared with standard counselling. The card was highly rated by patients as a welcome tool for self-monitoring. CONCLUSIONS: No beneficial effect on self-efficacy or dehydration markers with UCC use was demonstrated. The study nonetheless drew attention to several factors potentially hindering its use for effective self-care: the unexpected severity of other symptoms consuming patients' attention, reduced sensitivity of urine colour due to chemotherapy, absence of active inquiry by the healthcare team and the inconvenient location of the UCC in wallet/purse. Urine colour monitoring in patients with oesophageal cancer to improve the patient experience during treatment warrants further study but supported by active healthcare provider inquiry, more accessible format of the card, and possibly home vital checks to increase its sensitivity in the clinical context.

Adjuvant carboplatin and paclitaxel with "sandwich" method radiotherapy for stage III or IV endometrial cancer: long-term follow-up at a single-institution.

OBJECTIVE: To evaluate disease-free survival (DFS) and overall survival (OS) associated with adjuvant carboplatin and paclitaxel chemotherapy interposed with radiation for advanced endometrial cancer. METHODS: This is a cohort study of adult women with stage III or IV endometrial cancer treated at a single institution, between April 2002 and October 2017. Tumor and treatment characteristics were recorded. Treatment consisted of 4 cycles of intravenous paclitaxel and carboplatin every 3 weeks, followed by external beam radiotherapy to the pelvis (45-50 Gy), and another 2 cycles of chemotherapy. One cohort of patients were prospectively enrolled from 2002 through 2006 and an additional cohort from 2007 to 2017, which was retrospectively analyzed. Primary endpoints for this study were DFS and OS rates which were calculated using Cox regression models. RESULTS: Eighty-two patients with a median age of 66.5 years (range, 35-83 years) were included. Median follow-up was 46 months (range, 9-196 months). Most patients had stage IIIC disease (62.2%) and serous carcinoma histology (46.3%). Median OS was 146 months and median DFS was 71 months. A 5-year OS and DFS were 64.9% and 55.7%, respectively. Age >60 years subgroup was at a significantly higher risk of DFS event or death. Histological subtype, location of positive nodes, and cancer stage (IIIa vs. higher stage) did not correlate to a higher risk of recurrence or death. CONCLUSION: Long term follow-up and a larger population confirm that the chemoradiotherapy sandwich method yields favorable outcomes in patients with high-risk endometrial cancer.

Detection of Circulating Tumor DNA After Stereotactic Ablative Radiotherapy in Patients With Unbiopsied Lung Tumors (SABR-DETECT).

For patients with stage I/IIA non-small-cell lung cancer (NSCLC), surgical resection is the standard treatment. However, some of these patients are not candidates for surgery or refuse a surgical option. Definitive stereotactic ablative radiotherapy (SABR) is a standard approach in these patients. Approximately 15% of patients undergoing SABR for localized NSCLC will experience a recurrence within 2 years. Furthermore, many of these patients are deemed appropriate for SABR without a tissue diagnosis, based on the likelihood of malignancy which can be calculated by validated models. A liquid biopsy, detecting ctDNA, would be useful in early detection of recurrences, and documenting a cancer diagnosis in patients without a biopsy. This is a multi-institutional study enrolling patients with suspected stage I/IIA NSCLC and a pretreatment likelihood of malignancy of ≥60% using the validated models for patients without a tissue diagnosis, in cohort 1 (n = 45). The second cohort will consist of biopsied patients (n = 30-60). SABR will be delivered as per risk-adapted protocol. Plasma will be collected for ctDNA analysis prior to the first fraction of SABR, 24 to 72 hours after first fraction, and at 3, 6, 9, 12, 18, and 24-months. The patients will be followed up with imaging at 3, 6, 9, 12, 18, and 24-months. The primary objective is to assess whether a cancer detection liquid biopsy platform can predict recurrence of NSCLC. The secondary objectives are to assess the impact of SABR on detection rates of ctDNA in patients undergoing SABR and to correlate ctDNA positivity and pretreatment probability of malignancy (NCT05921474).

A Multi-Centre Randomized Study Comparing Two Standard of Care Chemotherapy Regimens for Lower-Risk HER2-Positive Breast Cancer.

BACKGROUND: Neither paclitaxel plus trastuzumab (P-H) nor docetaxel-cyclophosphamide plus trastuzumab (TC-H) have been prospectively compared in HER2-positive early-stage breast cancer (EBC). A randomized trial was performed to assess the feasibility of a larger study. METHODS: Lower-risk HER2-positive EBC patients were randomized to either P-H or TC-H treatment arms. The co-primary feasibility outcomes were: ≥75% patient acceptability rate, active trial participation of ≥50% of medical oncologists, ≥75% and ≥90% treatment completion, and receipt rate of planned cycles of chemotherapy, respectively. SECONDARY OUTCOMES: Febrile neutropenia (FN) rate, treatment-related hospitalizations, health-related quality of life (HR-QoL) questionnaires. Analyses were performed by per protocol and intention-to-treat. RESULTS: Between May 2019 and March 2021, 49 of 52 patients agreed to study participation (94% acceptability rate). Fifteen (65%) of 23 medical oncologists approached patients. Rates of FN were higher (8.3% vs. 0%) in the TC-H vs. P-H arm. Median (IQR) changes in scores from baseline in FACT-Taxane Trial Outcome Index at 24 weeks were -4 (-10, -1) vs. -6.5 (-15, -2) for TC-H and P-H arms, respectively. CONCLUSIONS: A randomized trial comparing P-H and TC-H was feasible. Expansion to a larger trial would be feasible to explore patient-reported outcomes of these adjuvant HER2 chemotherapy regimens.

Evaluation of Renal Function Recovery After Holmium Laser Enucleation of the Prostate in Patients with Chronic Kidney Disease.

Introduction: Holmium laser enucleation of the prostate (HoLEP) has become a new surgical gold standard treatment for benign prostatic hyperplasia (BPH). It is known that untreated BPH can lead to bladder outlet obstruction (BOO). A positive correlation exists between BOO and chronic kidney disease (CKD), but stability or recovery of renal function after HoLEP remains unknown. We sought to describe changes in renal function after HoLEP in men with CKD. Methods: A retrospective study was conducted of patients who underwent HoLEP with glomerular filtration rates (GFRs) <60, CKD stages III to V. Pre- and postoperative GFRs were selected within 3 months before the operation and within 1 year postoperatively. The presence of an indwelling catheter, preoperative hydronephrosis, history of kidney stones, and prostate size were also reviewed. Data were analyzed in accordance with preoperative CKD stage. Results: Of the reviewed patients, 138 met inclusion criteria with CKD stages III to V. Each CKD group was without significant postoperative complications. There was a significant increase between pre- and postoperative GFR for patients in CKD stages III (n = 116) and IV (n = 17) (p < 0.0001 and p = 0.010, respectively). The mean increase between pre- and postoperative GFR for the CKD stages III and IV patients were 6.4 and 6.49, respectively. There was no correlation between presence of preoperative hydronephrosis, history of kidney stones, catheter dependency, nor prostate size on change in postoperative GFR (p > 0.05). Conclusion: These findings suggest that patients in CKD stages III or IV undergoing HoLEP experience an increase in GFR. It is noteworthy that there appears to be no decline in renal function postoperatively in any group. HoLEP represents an excellent surgical option for patients with preoperative CKD and may prevent further renal decline.

Primary Prophylaxis Lapelga® in Early Breast Cancer: A Real-World Experience.

BACKGROUND: Lapelga® was approved by Health Canada as a pegfilgrastim biosimilar in 2019 and remains the most commonly used biosimilar in Ontario and is fully reimbursed under the Ontario Drug Benefit program in this category. We explored the efficacy and tolerability of Lapelga® in a retrospective analysis of patients with early breast cancer who underwent adjuvant chemotherapy supported with Lapelga® as a primary prophylaxis. METHODS: Adult patients with early breast cancer treated with adjuvant chemotherapy at the London Regional Cancer Program in London, ON, Canada between May 2019 and June 2022 were included. All of these patients were supported with Lapelga® as the primary prophylaxis. Patients' age, tumour, and nodal status, their type of chemotherapy, co-morbid conditions, and incidence of febrile neutropenia (FN) and its related details as well as any reported side effects to Lapelga® were collected. RESULTS: A total of 201 patients were included in this review with majority (78%) of patients under 65 years of age. One third of patients were treated with the adriamycin and cyclophosphamide (AC)-Paclitaxel dose dense chemotherapy and a quarter of patients with either a docetaxel and cyclophosphamide (TC) combination or an AC-dose dense with Paclitaxel weekly, and 10% or less patients had FEC-D (5-fluorouracil, epirubicin, and cyclophosphamide) and AC chemotherapy. FN incidence was only 3.48% in this review (7/201 patients). Patients with FN were admitted to hospital and recovered completely with no mortality reported. No cases of a switch to a different granulocyte colony growth factor were seen. The most frequent side effects from Lapelga® included musculoskeletal pain, fever, and headache. However, the majority of patients (88.6%; 178/201) did not have any reported side effects specifically assigned to Lapelga®. CONCLUSIONS: In this single centre retrospective study, early breast cancer patients (n = 201) treated with adjuvant chemotherapy supported with primary prophylaxis with Lapelga® had a low incidence of FN (3.48%). This supports Lapelga® being an effective strategy as the primary prophylaxis when used with common chemotherapy regimens in the real-world setting.

Metabolomic identification of predictive and early biomarkers of cisplatin-induced acute kidney injury in adult head and neck cancer patients.

AIM: Cisplatin causes acute kidney injury (AKI) in approximately one third of patients. Serum creatinine and urinary output are poor markers of cisplatin-induced AKI. Metabolomics was utilized to identify predictive or early diagnostic biomarkers of cisplatin-induced AKI. METHODS: Thirty-one adult head and neck cancer patients receiving cisplatin (dose ≥70 mg/m2 ) were recruited for metabolomics analysis. Urine and serum samples were collected prior to cisplatin (pre), 24-48 h after cisplatin (24-48 h) and 5-14 days (post) after cisplatin. Based on serum creatinine concentrations measured at the post timepoint, 11/31 patients were classified with clinical AKI. Untargeted metabolomics was performed using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Metabolic discrimination was observed between "AKI" patients and "no AKI" patients at all timepoints. Urinary glycine, hippuric acid sulfate, 3-hydroxydecanedioc acid and suberate were significantly different between AKI patients and no AKI patients prior to cisplatin infusion. Urinary glycine and hippuric acid sulfate were lower (-2.22-fold and -8.85-fold), whereas 3-hydroxydecanedioc acid and suberate were higher (3.62-fold and 1.91-fold) in AKI patients relative to no AKI patients. Several urine and serum metabolites were found to be altered 24-48 h following cisplatin infusion, particularly metabolites involved with mitochondrial energetics. CONCLUSIONS: We propose glycine, hippuric acid sulfate, 3-hydroxydecanedioc acid and suberate as predictive biomarkers of predisposition to cisplatin-induced AKI. Metabolites indicative of mitochondrial dysfunction may serve as early markers of subclinical AKI.

Clinical Factors and Outcomes When Real-World Heart Teams Overruled STS Risk Scores in TAVR Cases.

Objectives: This study was conducted to determine why heart teams recommended transcatheter aortic valve replacement (TAVR) versus surgical AVR (SAVR) for patients at low predicted risk of mortality (PROM) and describe outcomes of these cases. Background: Historically, referral to TAVR was based predominately on the Society of Thoracic Surgeons (STS) risk model's PROM >3%. In selected cases, heart teams had latitude to overrule these scores. The clinical reasons and outcomes for these cases are unclear. Methods: Retrospective data were gathered for all TAVR and SAVR cases conducted by 9 hospitals between 2013 and 2017. Results: Cases included TAVR patients with STS PROM >3% (n = 2,711) and ≤3% (n = 415) and SAVR with STS PROM ≤3% (n = 1,438). Leading reasons for recommending TAVR in the PROM ≤3% group were frailty (57%), hostile chest (22%), severe lung disease (16%), and morbid obesity (13%), and 44% of cases had multiple reasons. Most postoperative and 30-day outcomes were similar between TAVR groups, but the STS PROM ≤3% group had a one-day shorter length of stay (2.5 ± 3.4 vs. 3.5 ± 4.7 days; p ≤ 0.001) and higher one-year survival (91.6% vs. 86.0%, p=0.002). In patients with STS PROM ≤3%, 30-day mortality was higher for TAVR versus SAVR (2.0% vs. 0.6%; p < 0.001). Conclusions: Heart teams recommended TAVR in patients with STS PROM ≤3% primarily due to frailty, hostile chest, severe lung disease, and/or morbid obesity. Similar postoperative outcomes between these patients and those with STS PROM >3% suggest that decisions to overrule STS PROM ≤3% were merited and may have reduced SAVR 30-day mortality rate.

Rapid Antigen Screening of Students and Staff for SARS-CoV-2 in Rural School Districts, Pierce County, WA, 2020.

During fall 2020 in rural Pierce County, Washington, school districts and the county health department offered weekly rapid antigen screening to students and staff. Asymptomatic screening identified 42.5% of confirmed cases from the population. Parents reported it was a positive experience for their children. The program supported decisions to return to in-person learning, but screening ended because of resource and technical limitations. When planning in-school screening, stakeholder engagement and resource sustainability are important factors to consider. (Am J Public Health. 2022;112(8):1134-1137. https://doi.org/10.2105/AJPH.2022.306875).

An Electronic Information Kiosk for Enhancing Patient Accrual for Cancer Clinical Trials: A Pilot and Feasibility Study.

Introduction Low accrual to clinical trials for solid tumors at our institution led to a review of possible modifiable factors within our control. This led to a pilot project to determine whether improved patient awareness could alter accrual rates to active trials. Methods An information kiosk was located at the patient library on the ground floor of the London Regional Cancer Program. Adult cancer patients were invited to learn more about clinical trials from our research navigator, including specific trials open in our center, and to participate in the study, which involved a brief satisfaction and demographics survey. Results Three hundred and eighty-six (386) patients interacted with the clinical trial information kiosk over the eight weeks it was open. Of these, 32 patients consented and filled out surveys, which indicated an overall positive interaction with the kiosk. Unfortunately, in the time period examined, clinical trial accrual rates appeared to decrease when the pre- and post-kiosk activation periods were compared (44 versus 37 patients accrued to various trials). Conclusion Our pilot study found that the implementation of a clinical trial information kiosk was easy to understand and useful for patients to learn more about clinical trials. Barriers to this patient satisfaction translating into increased accrual rates in our center included suboptimal kiosk location and lack of guidance to the kiosk from clerical staff. High patient satisfaction scores support the potential value of permanent clinical trial information kiosks in our cancer center, but this requires increased attention to visibility, location, and staff education.

Pregnant People's Perspectives On Cannabis Use During Pregnancy: A Systematic Review and Integrative Mixed-Methods Research Synthesis.

INTRODUCTION: Rates of perinatal cannabis use are rising, despite clinical evidence about the potential for harm. Accordingly, pregnant and lactating people who perceive a benefit from cannabis use may have a difficult time making informed decisions about cannabis use. METHODS: We conducted a systematic review of mixed-methods research to synthesize existing knowledge on the perspectives of pregnant people and their partners about cannabis use in pregnancy. Six health and social science databases were searched up until May 30, 2021. There were no methodological, time, or geographic limits applied. We employed a convergent integrative approach to the inductive analysis of findings from all studies. RESULTS: We identified 26 studies describing views of 17,781 pregnant and postpartum people about cannabis use in pregnancy. No studies describing the views of partners were identified, and only one study specifically addressed the perspectives of lactating people. Comparative analysis revealed that whether cannabis was studied alone or grouped with other substances resulted in significant diversity in descriptions of participant decision-making priorities and perceptions of risks and benefits. Studies of cannabis alone demonstrated a complex decision-making process whereby perceived benefits are balanced against the available information about risk, which is often unclear and uncertain. Clear and helpful information was difficult to identify, and health care providers were not described as a helpful and trusted resource for decision-making. DISCUSSION: Decision-making about cannabis use is difficult for pregnant and lactating people who perceive a benefit from this use, although this decisional difficulty is seldom reflected in studies that examine cannabis as one of multiple substances that pregnant or lactating people may use. Our review suggests several approaches clinicians may take to encourage open and supportive conversations to facilitate informed decisions about cannabis use during the perinatal period.

Exploitation of treatment induced tumor lysis to enhance the sensitivity of ctDNA analysis: A first-in-human pilot study.

INTRODUCTION: Blood-based liquid biopsies examining circulating tumour DNA (ctDNA) have increasing applications in non-small cell lung cancer (NSCLC). Limitations in sensitivity remain a barrier to ctDNA replacing tissue-based testing. We hypothesized that testing immediately after starting treatment would yield an increased abundance of ctDNA in plasma because of tumor lysis, allowing for the detection of genetic alterations that were occult in baseline testing. METHODS: Three prospective cohorts of patients with stage III/IV NSCLC were enrolled. Cohort 1 (C1) contained patients starting platinum doublet chemoradiation (n = 10) and cohort 2 (C2) initiating platinum doublet cytotoxic chemotherapy ± immunotherapy (n = 10). Cohort 3 (C3) contained patients receiving palliative radiation. Two baseline samples were collected. In C1 and C2, subsequent samples were collected 3, 6, 24 and 48 h post initiation of chemotherapy. Patients in C3 had samples collected immediately prior to the next three radiotherapy fractions. Samples were analyzed for ctDNA using the 36-gene amplicon-based NGS Inivata InVisionFirst®-Lung assay. RESULTS: A total of 40 patients were enrolled. Detectable ctDNA was present at baseline in 32 patients (80%), 4 additional patients (50%) had detectable ctDNA in post-treatment samples. Seven patients with detectable ctDNA at baseline (23%) had new genetic alterations detected in post-treatment samples. Mutant molecule numbers increased with treatment in 24 of 31 (77%) pts with detectable ctDNA. ctDNA levels peaked a median of 7 h (IQR:2-26 h) after the initiation of chemotherapy and a median of 2 days (IQR:1-3 days) after radiation was commenced. CONCLUSION: ctDNA levels increase in the hours to days after starting treatment. ctDNA testing in the acute post-treatment phase can yield results that were not evident in pre-treatment testing. Application of this principle could improve ctDNA utility as an alternate to tissue-based testing and improve sensitivity for the detection of treatment-resistant clones.(NCT03986463).

Clinician responses to cannabis use during pregnancy and lactation: a systematic review and integrative mixed-methods research synthesis.

BACKGROUND: Perinatal cannabis use is increasing, and clinician counselling is an important aspect of reducing the potential harm of cannabis use during pregnancy and lactation. To understand current counselling practices, we conducted a systematic review and integrative mixed-methods synthesis to determine "how do perinatal clinicians respond to pregnant and lactating patients who use cannabis?" METHODS: We searched 6 databases up until 2021-05-31. Eligible studies described the attitudes, perceptions, or beliefs of perinatal clinician about cannabis use during pregnancy or lactation. Eligible clinicians were those whose practice particularly focusses on pregnant and postpartum patients. The search was not limited by study design, geography, or year. We used a convergent integrative analysis method to extract relevant findings for inductive analysis. RESULTS: Thirteen studies were included; describing perspectives of 1,366 clinicians in 4 countries. We found no unified approach to screening and counselling. Clinicians often cited insufficient evidence around the effects of perinatal cannabis use and lacked confidence in counselling about use. At times, this meant clinicians did not address cannabis use with patients. Most counselled for cessation and there was little recognition of the varied reasons that patients might use cannabis, and an over-reliance on counselling focussed on the legal implications of use. CONCLUSION: Current approaches to responding to cannabis use might result in inadequate counselling. Counselling may be improved through increased education and training, which would facilitate conversations to mitigate the potential harm of perinatal cannabis use while recognizing the benefits patients perceive.

Cannabis use during pregnancy and breastfeeding is common and understanding current physician counselling approaches is important to identify gaps and to make suggestions for practice. We conducted a systematic review of the literature to understand how physicians respond to pregnant or breastfeeding patients who use cannabis. We found 13 eligible articles in our review and our analysis showed that there was no common approach to screening and counselling patients. Physicians often described needing more training and education to support their confidence. Additionally, physicians often did not address the various medical reasons for which patients might use cannabis during pregnancy and breastfeeding. We suggest that counselling approaches may be improved through increased education and training. This could facilitate conversations to help mitigate the potential harm of cannabis use while recognizing the benefits patients perceive and thus establish strong patient­physician relationships.

Detection of Circulating Tumor DNA in Patients with Thyroid Nodules.

OBJECTIVE: Detection of circulating tumor DNA (ctDNA) in cancer patients can potentially serve as a noninvasive, sensitive test of disease status. The purpose of this study was to determine the ability to detect BRAF (V600E) mutations in the plasma of patients with thyroid nodules, with the goal of distinguishing between benign and malignant nodules. METHODS: Consecutive patients with thyroid nodules who consented for surgery were recruited. Plasma samples were obtained preoperatively and one month postoperatively. Quantitative PCR was used to determine the levels of the BRAF (V600E) mutation preoperatively and postoperatively. RESULTS: A total of 109 patients were recruited. On final pathology, 38 (32.8%) patients had benign thyroid nodules, 45 (38.8%) had classical papillary thyroid cancer (PTC), 23 (19.8%) had nonclassical PTC, and 3 (2.6%) had follicular thyroid cancer. 15/109 patients had detectable BRAF (V600E) ctDNA in their preoperative samples-all of them having classical PTC. Higher T-stage and extrathyroidal extension in PTC were associated with positive BRAF (V600E) ctDNA (p < 0.05). Eighty-eight pairs of preoperative and postoperative plasma samples were collected and analyzed. Of these eighty-eight paired samples, a total of 13/88 (14.8%) patients had detectable BRAF (V600E) ctDNA in their preoperative samples-all of them having classical PTC. 12 of these 13 patients had no detectable BRAF (V600E) postoperatively, while one remaining patient had a significant decline in his levels (p < 0.05). CONCLUSION: BRAF (V600E) circulating thyroid tumor DNA can be detected in plasma and is correlated with a final diagnosis of the classical variant of PTC. Given that a postoperative drop in BRAF (V600E) ctDNA levels was observed in all cases suggests its utility as a tumor marker.

The sources and prevalence of anthropogenic noise in Rockfish Conservation Areas with implications for marine reserve planning.

Underwater noise pollution is a recognized threat to marine life. In British Columbia, Canada, Pacific rockfish (Sebastes spp.) were historically overfished, prompting the establishment of Rockfish Conservation Areas (RCAs). However, there are no restrictions prohibiting vessel transits in RCAs. We hypothesized that RCAs do not protect rockfish from sub-lethal harm from noise. We compared noise levels at three RCAs with adjacent unprotected reference sites from August 2018-June 2019. While RCAs had lower levels of noise overall than reference sites, this trend was inconsistent; some RCA sites had higher levels of noise during certain time periods than non-RCA sites. A vessel noise detector was the best predictor of noise level over three frequency bands (20-100 Hz, 100-1000 Hz, 1-10 kHz), and predicted sound levels which could mask rockfish communication. We conclude that RCAs do not reliably protect rockfish from noise pollution, and recommend further study into potential impacts on stock recovery.

FishCam: A low-cost open source autonomous camera for aquatic research.

We describe the "FishCam", a low-cost ( < 500 USD) autonomous camera package to record videos and images underwater. The system is composed of easily accessible components and can be programmed to turn ON and OFF on customizable schedules. Its 8-megapixel camera module is capable of taking 3280 × 2464-pixel images and videos. An optional buzzer circuit inside the pressure housing allows synchronization of the video data from the FishCam with passive acoustic recorders. Ten FishCam deployments were performed along the east coast of Vancouver Island, British Columbia, Canada, from January to December 2019. Field tests demonstrate that the proposed system can record up to 212 h of video data over a period of at least 14 days. The FishCam data collected allowed us to identify fish species and observe species interactions and behaviors. The FishCam is an operational, easily-reproduced and inexpensive camera system that can help expand both the temporal and spatial coverage of underwater observations in ecological research. With its low cost and simple design, it has the potential to be integrated into educational and citizen science projects, and to facilitate learning the basics of electronics and programming.

Strategies to Mitigate Anxiety and Pain in Intrauterine Device Insertion: A Systematic Review.

One barrier to the use of intrauterine devices (IUDs) as a contraceptive method is the experience of anxiety and pain during the insertion procedure. Previous reviews have focused on pharmacological methods used to relieve pain during IUD insertion; however, few similar reviews have examined non-pharmacological methods to relieve pain or strategies to reduce anxiety. The objectives of this study were to identify and categorize strategies for reducing anxiety and pain with respect to IUD insertion and the ways in which anxiety and pain were assessed. In particular, the study aimed to identify non-pharmacological interventions and studies that included anxiety as a research outcome. A literature search was conducted of all English-language studies between inception and the week of July 29, 2018 from the following online databases: Medline, Embase, Cochrane Library, and PubMed. The search revealed 426 studies after removal of duplicates, 35 of which fulfilled the inclusion criteria. A total of 29 studies were identified as assessing pharmacological interventions for the management of pain, and six studies assessed non-pharmacological interventions. Only one study included a measurement of patient anxiety during the procedure as an outcome measure. Research on non-pharmacological interventions for the management of anxiety and pain during IUD insertion is lacking. This review found that evidence for the studied pharmacological interventions is conflicting, and there is very little evidence on understanding the effectiveness of strategies to manage anxiety during the IUD insertion procedure. Further high-quality research on non-pharmacological pain and anxiety management strategies is warranted.

Spleen tyrosine kinase expression is correlated with human papillomavirus in head and neck cancer.

OBJECTIVES: Spleen tyrosine kinase (SYK) is a promoter of cell survival in a variety of cell types, including normal and cancerous epithelial cells. We hypothesized that SYK would an important therapeutic target to inhibit for the treatment of HNSCC. MATERIALS AND METHODS: SYK protein abundance in patient tumours was evaluated. SYK protein and mRNA abundance was used to examine patient survival and human papillomavirus (HPV) status. Small-interfering RNAs and gene editing with CRISPR/Cas9 were used to evaluate SYK expression on proliferation in HNSCC cell lines. The potency of SYK inhibitor ER27319 maleate on cellular proliferation was tested using a panel of 28 HNSCC cell lines and in vivo in HNSCC patient-derived xenograft (PDX) models. RESULTS: Moderate to high protein expression of SYK was observed in 24% of patient tumors and high SYK expression was exclusively observed in HPV-positive samples (p < 0.001). SYK inhibition with RNA interference, gene editing or a SYK inhibitor (ER27319) decreased cell proliferation and migration. Treatment of PDXs with ER27319 maleate was observed to reduce tumour burden in vivo in two of three models. CONCLUSIONS: HPV-positive HNSCC harbours high SYK protein levels. We demonstrate that proliferation, migration and overall burden of these tumours can be reduced by genetic or pharmacologic inhibition of SYK. Taken together, these data establish SYK as a therapeutic target for HNSCC.